In the past several decades, both the incidence and the types of fungus infection severely detrimental to human health were continuously increased, especially for the immunosuppressed patients. At the same time, the clinical application of certain commonly used clinical antifungal agents, such as amphotericin, imidazoles and triazoles commonly used clinically, was restricted due to significant neurotoxicity, drug resistance, and the like. Echinocandins, as a kind of novel antifungal agents, are a group of natural products discovered in the 1970s. Structurally, the echinocandins have a similar cyclic polypeptide core but have different fatty acid side chains. Echinocandins can competitively inhibit the synthesis of β-D-glucan in fungal cell walls. The advantages of echinocandins are low toxicity, strong fungicidal activity, and as well as excellent pharmacokinetic properties.
Echinocandins family includes the following membersechinocandins, cilofungin, pneumocandins, aculeacins, mulundocandin, and WF11899A. Echinocandins and pneumocandins have been actively investigated and are currently applied clinically.
Caspofungin is a water-soluble semi-synthetic derivative of pneumocandin. Merck developed caspofungin as an anti-fungus/pneumocystis agent with a broad spectrum. In a phase II clinical trial with control experiments, it was found that, for the immunosuppressed patients suffering from invasive pulmonary aspergillosis, caspofungin administration (intravenous injection, 50-70 mg/d) achieved good efficacy while administrating amphotericin B and azoles comprising nitrogen did not show any obvious effect. In the 128 cases of HIV infected patients, the efficiency of caspofungin for monilial esophagitis reached 85%, while amphotericin B only had the efficiency of 66.7%. These kinds of drugs can be used to effectively kill fungi which are resistant to azoles comprising nitrogen and amphotericin B. Moreover, these kinds of drugs are superior to traditional antifungal gents, due to the none-hemolytic toxicity and less drug interaction.

Structure of Caspofungin
Pneumocandin is a class of natural antifungal drugs produced by Glarea lozoyensis. It can be primarily classified into three types according to the different substituents on the proline in its structure: A0 (3-hydroxyl-4-methylproline), B0 (3-hydroxylproline) and C0 (4-hydroxylproline). Moreover, according to the different substituents on the cyclic polypeptides, pneumocandin A0 can be subclassified into six subtypes: A0, A1, A2, A3, A4, and A5; B0 can be subclassified into six subtypes, B0, B1, B2, B3, B4, B5; wherein A0, A1, A3, A4, and B0 are produced by the wild-type strain ATCC20868, with Ao being the major one. Through NMU mutagenesis of ATCC20868, a mutant strain ATCC20957 was obtained which is able to produce A0 and B0 simultaneously. However, ATCC20957 produces B0 with a relatively low capacity, and A0 is produced as an impurity in a relatively high quantity.
Accordingly, it is urgent to find a strain with stable genetic and high-yield properties which can produce more B0 and less A0 for fulfilling the requirements of industrial production.